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Referral of the month – hypothyroidism

Dear consultant,

Thank you for seeing this lady with hypothyroidism. She was diagnosed two years ago when she presented with malaise and some weight gain, and was found to be biochemically hypothyroid (on repeat blood testing).

Despite repeated manipulation of her thyroxine dosage and assurances that she is complying with treatment, we cannot seem to reach consistently satisfactory TFTs. Indeed, quite minor changes in her thyroxine dose seem to result in dramatic biochemical fluctuations, and we have reached a state of mutual exasperation.

In addition, she is disappointed that, despite her treatment, she feels as unwell as ever. She has joined an internet forum and has become convinced that all her problems would be solved if I prescribed her T3, which I have so far resisted. I would appreciate your view on this.

She is on no other medication and has no other significant medical history.

Yours sincerely, GP

Dear GP,

It was a pleasure to see Mrs A in my endocrine clinic again today. You will recall that I first met her four months ago when you referred her with symptoms of persistent lethargy and difficult control of hypothyroidism.

At the time she had been markedly frustrated by her symptoms and had inquired specifically about T3, which she had researched extensively on the internet.

At the initial visit I had reviewed her thyroxine therapy. She was on an adequate dose for her body weight and her tablets were dispensed from the same pharmacy and were consistent in brand. She was not taking other medications that could interfere with thyroxine absorption. She claimed good medication compliance, but admitted that due to her busy schedule she took her tablet at various times each day often with coffee or a glass of wine in the evenings.

She reported sleeping poorly and being constantly exhausted. Although she denied feeling low in mood, she admitted to a hectic schedule balancing the demands of a full-time job and caring for three young children. As a result she had given up walking, which she previously enjoyed and had since observed a gradual increase in weight.

At the review four months ago, I had advised her to take her tablets on an empty stomach with water. I had also stressed the need for thyroxine to be administered at a constant time each day, ideally first thing in the morning or last thing before bed, as this allows greater stability in thyroid status. Lastly we had discussed the potential benefits of a healthier diet and physical activity on her general wellbeing.

Today, I was pleased to see that she has joined a gym and resumed regular walking. She has lost an impressive 3kg in weight and now grades her lethargy as mild compared to severe. We reviewed the blood tests I had earlier requested for potential causes of lethargy. These have all returned negative, including screens for coeliac disease, diabetes, anaemia, Addison’s disease, and vitamin B12 and vitamin D deficiencies.

She is now taking her tablets correctly and it was reassuring to see that her TSH level is now within the lower half of the laboratory reference range. She is on a stable thyroxine dose and I would suggest that future dose changes should only be considered after careful review of common factors that affect thyroxine dose, such as poor compliance, incorrect tablet administration, and concomitant use of medications like iron and antacids.

Today we revisited the issue of T3 therapy. As you know, current guidelines do not support routine use of T3 in hypothyroidism and evidence from controlled trials has shown no added benefit of combined therapy with T3 and thyroxine over thyroxine therapy alone, although some experts will occasionally consider a trial of T3 under strict supervision in carefully selected patients. Today she was clearly less enthusiastic about T3 than previously, and agreed to persevere with the lifestyle changes that have proven effective.

I have provided her with literature on hypothyroidism and advised her to be wary of unregulated internet health advice. While many websites provide factual information, a number are inaccurate and misleading. I have directed her to the website of the British Thyroid Foundation.

She seemed satisfied with her progress and is happy to be discharged back to your care. I have not arranged another appointment but would be happy to see her again if problems arise in future.

Why do a persistent minority of hypothyroid patients continue to complain of ill health on levothyroxine? This referral doesn't reflect the reality of many GP's experience. Is it realistic to expect one treatment option to suit all hypothyroid patients when the condition has multiple causes and complex aetiogy.

"evidence from controlled trials has shown no added benefit of combined therapy with T3 and thyroxine over thyroxine therapy alone."

Actually that's not the case. If you read the details of various blinded RCTs conducted over the years, in a number of them, patients were found to prefer T3+T4 combination therapy over T4 therapy. In some there were benefits such as increased weigh loss and improved outcomes on QOL measures in the T3+T4 groups over T4-only.

Patients are all different, only in fantasy-land do you get standardised "textbook cases" Treat the patient, not the number.

The 'dramatic biochemical fluctuations' appear to have been laid at the patient's door. The patient was taking her levothyroxine 'often with coffee'. She was advised to take her tablets with water but not to refrain from coffee, which might well accompany her breakfast. (Altered intestinal absorption of L-thyroxine caused by coffee. Benvenga S et al 2008 Thyroid 18(3):293-301.)Achieving a TSH in the lower half of the laboratory reference range may not be sufficient. In particular it misses the inverse log TSH / thyroid hormone relationship. Guidance on combined therapy is based on studies of patients with primary hypothyroidism that target typical serum fT3 / fT4 ratios. In practice patients often find a higher level of fT3 effective in resolving symptoms without provoking signs of thyrotoxicity. Such patients may have other thyroid issues such as thyroid hormone disruption by environmental toxins. Current guidance is based on studies of patients with unequivocal primary hypothyroidism and is applicable only to those with primary hypothyroidism. This patient 'was found to be biochemically hypothyroid (on repeat blood testing)'. It is likely that this patient's symptoms of hypothyroidism are to some extent a consequence of impaired thyroid hormone action rather than just low serum hormone levels. In this case guidelines for treatment of primary hypothyroidism should not apply. It is unlikely the profound symptoms are a result of marginal thyroid failure as indicated by the need for repeat blood testing.

Levothyroxine has half life of about 7 days . Does it really matter what time of the day the tablet is taken?There are trial of once weekly regimes for patients with poor compliance, with good results.

The thyroxine made no difference to the way I was feeling when I started it, but this does not seem to be a measure that doctors (GPs or consultants) feel important, despite it being very important to patients. I didn't feel ill (apart from palpitations at the start of the disease when I was overactive, prior to becoming underactive) but it was found during a routine blood test as I am on metformin for PCOS - purely chance.

It makes no difference to the way you feel if you miss a day (or two), take it with water, tea, juice, before or after breakfast, etc.

My bloods are largely stable (the measure for doctors to use).

My various joint/muscle aches may be thyroid disease related, or may be down to another issue for which I have a "probable" diagnosis. (Something rare - I have many characteristics but not enough to tick the firm diagnosis boxes). Or something completely different, but seem to be managed by pregabalin with paracetamol and ibuprofen chucked in as needed.

Proud to say I am managed well, feel fine most of the time and work full time (and I rattle). I also get a few hours zumba in a week and cycle a little bit.

What I can tell you is that patients don't give a damn about what bloods tell you, what studies tell you and personally what label I have - most just want to feel better. If that means a trial of something that has a shaky wisp of evidence, so be it - you're managing people first, disease second.

Levothyroxine made me feel so ill and upon starting NDT myself I have felt so much better, despite it being early days. "Health care professionals" complaining on here about thyroid patients complaining shouldn't be working in a caring professionals unless they are prepared to listen to their symptoms and take a more holistic approach. However, the only way I think certain people will develop any empathy for those with hypothyroidism is if they themselves are struck down with it. Thyroid diseases are awful to live with and I know hundreds who would agree with me.

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